The macrophage-derived motor protein KIF13B enhances MERTK-mediated efferocytosis and prevents atherosclerosis in mice

作者：Yitong Xu, Jingxuan Chen, Yiran Liu, Ge Zhang, Guolin Miao, Jingdong Wu, Kaikai Lu, Yinqi Zhao, Wenxi Zhang, Liwen Zheng, Lianxin Zhang, Jinxuan Chen, Zihao Zhou, Yufei Han, Pingping Lai, Jiabao Guo, Donghui Wu, Si Mei, Ling Zhang, Yang Zhao, Wei Huang, Yuhui Wang, Junnan Tang, Dongyu Zhao, Xunde Xian · 发表于：European Heart Journal · 年份：2025 · DOI：10.1093/eurheartj/ehaf523 · 被引用次数：10 · 研究领域：Microtubule and mitosis dynamics、Phagocytosis and Immune Regulation、Hereditary Neurological Disorders

BACKGROUND AND AIMS: Atherosclerosis is a chronic inflammatory disorder with high morbidity and mortality rates worldwide. Emerging evidence has reported that kinesin family member 13B (KIF13B), a crucial motor protein, integrates hepatic lipid metabolism and inflammatory response to protect liver disease. However, the relationship between KIF13B and atherosclerosis remains unknown. The present study aimed to elucidate the specific role of KIF13B in atherosclerosis and its potential therapeutic significance. METHODS: The investigation first assessed the relationship between the expression levels of KIF13B and the progression of atherosclerosis in human cohort data and carotid plaques from patients. Subsequently, the authors generated Kif13b knockout (Kif13b-/-) mice on low-density lipoprotein receptor (Ldlr)-deficient background (Ldlr-/-) to obtain double knockouts (Kif13b-/-;Ldlr-/-) and myeloid-specific Kif13b knockout mice (Lyz2 Cre;Kif13bf/f) with adeno-associated virus 8 (AAV8)-mediated overexpression of proprotein convertase subtilisin/kexin type 9 (PCSK9). Moreover, Ldlr-/- mice received bone marrow transplants from either Kif13b-/-;Ldlr-/- or Ldlr-/- mice and were fed a Western diet (WD) for 12 weeks. RESULTS: KIF13B expression was significantly reduced in patients with atherosclerosis and negatively associated with the severity of atherosclerotic progress in WD-fed Ldlr-/- mice. In contrast to Kif13b-/-;Ldlr-/- mice showing a significant increase in plasma total chol...